Integrative Molecular Characterization of Malignant Pleural Mesothelioma

Authors: Julija Hmeljak, Francisco Sánchez-Vega, Katherine A. Hoadley, Juliann Shih, Chip Stewart, David I. Heiman, Patrick Tarpey, Ludmila Danilova, Esther Drill, Ewan A. Gibb, Reanne Bowlby, Rupa S. Kanchi, Hatice U. Osmanbeyoglu, Yoshitaka Sekido, Jumpei Takeshita, Yulia Newton, Kiley Graim, Manaswi Gupta, Carl M. Gay, Lixia Diao, David L. Gibbs, Vésteinn Thórsson, Lisa Iype, Havish S. Kantheti, David T. Severson, Gloria Ravegnini, Patrice Desmeules, Achim A. Jungbluth, William D. Travis, Sanja Đačić, Lucian R. Chirieac, Françoise Galateau-Sallé, Junya Fujimoto, Aliya N. Husain, Henrique C.S. Silveira, Valerie W. Rusch, Robert C. Rintoul, Harvey I. Pass, Hedy L. Kindler, Marjorie G. Zauderer, David J. Kwiatkowski, Raphael Bueno, Anne S. Tsao, Jenette Creaney, Tara M. Lichtenberg, Kristen Leraas, Jay Bowen, Ina Felau, Jean C. Zenklusen, Rehan Akbani, Andrew D. Cherniack, Lauren A. Byers, Michael S. Noble, Jonathan A. Fletcher, A. Gordon Robertson, Ronglai Shen, Hiroyuki Aburatani, B. W. Robinson, Peter J. Campbell, Marc Ladanyi, Hiroyuki Aburatani, Rehan Akbani, Adrian Ally, Pavana Anur, Joshua Armenia, J. Todd Auman, Miruna Balasundaram, Saianand Balu, Stephen B. Baylin, Michael J. Becich, Carmen Behrens, Rameen Beroukhim, Craig M. Bielski, Tom Bodenheimer, Moiz S. Bootwalla, Jay Bowen, Reanne Bowlby, Denise Brooks, Raphael Bueno, Lauren Averett Byers, Flavio Mavignier Cárcano, Rebecca Carlsen, André Lopes Carvalho, Andrew D. Cherniack, Dorothy Cheung, Lucian R. Chirieac, Juok Cho, Eric Chuah, Sudha Chudamani, Carrie Cibulskis, Leslie Cope, Daniel Crain, Jenette Creaney, Erin Curley, Sanja Đačić, Ludmila Danilova, Assunta De Rienzo, Timothy Defreitas, John A. Demchok, Noreen Dhalla, Rajiv Dhir, Lixia Diao, Esther Drill, Ina Felau, Michaël Feldman, Martin L. Ferguson, Jonathan A. Fletcher, Junya Fujimoto, Junya Fujimoto, Shiro Fukuda, Stacey Gabriel, Françoise Galateau-Sallé, Jianjiong Gao, Johanna Gardner, Julie M. Gastier-Foster, Carl M. Gay, Nils Gehlenborg, Mark Gerken, Gad Getz, Ewan A. Gibb, David L. Gibbs, Chandra Goparaju, Kiley Graim, Benjamin Groß, Guangwu Guo, Manaswi Gupta, Seiki Hasegawa, David Haussler, D. Neil Hayes, David I. Heiman, Zachary Heins, Julija Hmeljak, Katherine A. Hoadley, Robert A. Holt, Alan P. Hoyle, Aliya N. Husain, Carolyn M. Hutter, Lisa Iype, Stuart R. Jefferys, Steven J.M. Jones, Corbin D. Jones, Rupa S. Kanchi, Katayoon Kasaian, Jaegil Kim, Hedy L. Kindler, Nobuyuki Kondo, Thomas Krausz, Ritika Kundra, Kozo Kuribayashi, David J. Kwiatkowski, Marc Ladanyi, Phillip H. Lai, Peter W. Laird, Michael S. Lawrence, Darlene Lee, Kristen Leraas, Tara M. Lichtenberg, Pei Lin, Jia Liu, Wenbin Liu, Eric Minwei Liu, Laxmi Lolla, Adhemar Longatto‐Filho, Yiling Lu, James D. Luketich, Yussanne Ma, Dennis T. Maglinte, David Mallory, Marco A. Marra, Michael Mayo, Sam Meier, Jonathan Melamed, Shaowu Meng, Matthew Meyerson, Piotr A. Mieczkowski, Gordon B. Mills, Richard A. Moore, César A. Moran, Scott Morris, Lisle E. Mose, Andrew J. Mungall, Karen Mungall, Takashi Nakano, Rashi Naresh, Yulia Newton, Michael S. Noble, Angelica Ochoa, Hatice U. Osmanbeyoglu, Joel S. Parker, Harvey I. Pass, Joseph Paulauskis, Arjun Pennathur, Nathan A. Pennell, Robert Penny, Charles M. Perou, Todd Pihl, Nilsa C. Ramirez, Doris M. Rassl, Gloria Ravegnini, Glen Reid, Rui Manuel Reis, Sheila M. Reynolds, David C. Rice, William G. Richards, Robert C. Rintoul, Jeffrey Roach, A. Gordon Robertson, Valerie W. Rusch, Sara Sadeghi, Gordon Saksena, Francisco Sánchez-Vega, Chris Sander, Ayuko Sato, Cristovam Scapulatempo‐Neto, Jacqueline E. Schein, Nikolaus Schultz, Steven E. Schumacher, Tanguy Y. Seiwert, Yoshitaka Sekido, David T. Severson, Candace Shelton, Troy Shelton, Ronglai Shen, Robert L. Sheridan, Yan Shi, Juliann Shih, Yuichi Shiraishi, Ilya Shmulevich, Henrique C.S. Silveira, Janae V. Simons, Payal Sipahimalani, Tara Skelly, Heidi J. Sofia, Matthew G. Soloway, Paul T. Spellman, Chip Stewart, Joshua M. Stuart, Qiang Sun, Jumpei Takeshita, Angela Tam, Donghui Tan, Roy Tarnuzzer, Kenji Tatsuno, Barry S. Taylor, Nina Thiessen, Eric Thompson, Vésteinn Thórsson, William D. Travis, Anne S. Tsao, Kane Tse, Tohru Tsujimura, Federico Valdivieso, David Van Den Berg, Nico van Zandwijk, Umadevi Veluvolu, Luciano de Souza Viana, Douglas Voet, Yunhu Wan, Zhining Wang, Jing Wang, Joellen Weaver, John N. Weinstein, Daniel J. Weisenberger, Matthew D. Wilkerson, Lisa Wise, Ignacio I. Wistuba, Tina Wong, Ye Wu, Shogo Yamamoto, Liming Yang, Marjorie G. Zauderer, Jean C. Zenklusen, Jiashan Zhang, Hailei Zhang, Hongxin Zhang, Erik Zmuda - Cancer Discovery 2018 cited by 618

Abstract Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options. Significance: Through a comprehensive integrated genomic study of 74 MPMs, we provide a deeper understanding of histology-independent determinants of aggressive behavior, define a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expression of the immune-checkpoint gene VISTA in epithelioid MPM. See related commentary by Aggarwal and Albelda, p. 1508. This article is highlighted in the In This Issue feature, p. 1494